Two processes have been studied that may regulate angiotensin-I converting enzyme (ACE) activity. One process involves the control of intrinsic molecular activity by endogenous inhibitors. A second process involves hormonal control of a unique ACE isozyme in testis. The endogenous inhibitor(s) is soluble, dialyzable and heat stable under conditions favoring low oxygen tension. It appears to be a sulfhydryl-containing compound as N-ethylmaleimide blocks its activity and it is readily oxidizable. The inhibitor has not yet been isolated nor have many of its molecular characteristics been described. Testis provides a good model to study hormonal control of tissue levels of ACE. In the rat, the pituitary is essential for the development and maintenance of a unique isozyme of ACE that occurs in testes. This isozyme shares a certain degree of amino acid sequence homology with the well-described pulmonary enzyme, but is about 55,000 daltons smaller. The smaller testicular isozyme is less thermally stable than its larger pulmonary counterpart and this characteristic may affect its rate of renewal by rendering it more susceptible to proteolysis. Once the testicular isozyme has been allowed to disappear following hypophysectomy (either pre-pubescently or in mature rats), it is difficult to re-initiate synthesis with gonadotropins or androgen. However, if hormone replacement is started on the first day following hypophysectomy, follicle stimulating hormone/luteinizing hormone combination or testosterone, but not human chorionic gonadotropin, can prevent the loss of testicular ACE activity. These results, in combination with studies performed on purified cell populations from the testes, suggest that testicular ACE is associated with cells of the seminiferous tubules, most probably geminal cells.